<!--#if expr="$title" --> <!--#echo var="title" --> <!--#else --> HIV Drug Resistance Database <!--#endif -->
Stanford University HIV Drug Resistance Database - A curated public database designed to represent, store, and analyze the divergent forms of data underlying HIV drug resistance.

MARVEL on RT mutations at position 210


HIVdb Algorithm: Comments & Scores
  • L210F/S are rare mutations not associated with NRTI-resistance.
  • L210W usually occurs in combination with M41L and T215Y. The combination of M41, L210W and T215Y causes high-level resistance to AZT and d4T and intermediate to high-level resistance to ddI, ABC and TDF.

Mutation3TCFTCABCAZTD4TDDITDF
L210W551015151010
Footnote:Mutation scores on the left are derived from published literature linking mutations and ARVs (the complete details can be found in the HIVdb Release Notes).
Genotype-treatment correlation
Mutation frequency according to subtype and drug-class experience.
The frequency of each mutation at position 210 according to subtype and drug-class experience. Data are shown for the 8 most common subtypes. The number of persons in each subtype/treatment category is shown beneath the subtype. Mutations occurring at a frequency >0.5% are shown. Each mutation is also a hyper-link to a separate web page with information on each isolate, including literature references with PubMed abstracts, the GenBank accession number, and complete sequence and treatment records.

PosWTRTI Naive Persons NRTI (but no NNRTI) Treated Persons
A
5908
B
37839
C
11132
D
1662
F
1155
G
1327
AE
10362
AG
3905
 
A
286
B
4182
C
1225
D
120
F
80
G
137
AE
342
AG
81
210 L S 0.2
M 0.2
F 0.1
F 0.7
M 0.4
S 0.1
F 0.2
S 0.1
M 0.2
F 0.1
I 0.1
M 0.6
W 0.1
V 0.1
M 0.2
P 0.1
Y 0.1
M 1.7
F 0.6
S 0.3
W 0.1
M 0.4
Q 0.1
 W 1.9
F 0.8
S 0.4
M 0.4
I 0.4
W 18
F 0.7
S 0.1
G 0.1
W 1.7
F 0.4
S 0.2
W 4.8 W 9.2
M 1.3
V 1.3
W 5.2
S 0.7
W 15
F 0.6
M 0.6
W 3.8
Footnote: The query page Mutation Prevalence According to Subtype and Treatment to examine the frequency of all mutations according to subtype and treatment; The program HIVSeq provides similar output for mutations in user-submitted sequences; A complete description of the program that generates these tables can be found at Rhee et al AIDS 2006.
 

Mutation frequency according to treatment with individual ARVs.
The first row shows the frequency of the mutation in persons who are RTI-naive (indicated in green). The second row shows the frequency of the mutation in persons who have received one or more NRTIs (+/- NNRTIs). The following rows show the frequency of the mutation in persons who have received only a single NRTI. Mutation rates that differ significantly between treated and untreated isolates are indicated in yellow.
MutationNRTINNRTINumSeqNumMut% Mutantp
L210A008537230.00 
L210A>=1>=03810470.000.019
L210AAZT>=04720  
L210ADDI>=0540  
L210AD4T>=0550  
L210AABC>=0500  
L210AD4T+3TC>=045310  
L210AAZT+3TC>=0364820.000.003
L210AD4T+DDI>=04740  
L210AAZT+DDI>=07160  
L210AABC+3TC>=059810.100.005
L210ATDF+3TC>=0250510.000.246
L210ATDF+FTC>=013040  
MutationNRTINNRTINumSeqNumMut% Mutantp
L210E008537270.00 
L210E>=1>=03810470.000.207
L210EAZT>=04720  
L210EDDI>=0540  
L210ED4T>=0550  
L210EABC>=0500  
L210ED4T+3TC>=045310  
L210EAZT+3TC>=036480  
L210ED4T+DDI>=04740  
L210EAZT+DDI>=07160  
L210EABC+3TC>=05980  
L210ETDF+3TC>=0250510.000.563
L210ETDF+FTC>=013040  
MutationNRTINNRTINumSeqNumMut% Mutantp
L210F00853725640.60 
L210F>=1>=0381042710.700.335
L210FAZT>=047210.200.359
L210FDDI>=0540  
L210FD4T>=05523.600.059
L210FABC>=0500  
L210FD4T+3TC>=04531230.500.250
L210FAZT+3TC>=03648180.400.262
L210FD4T+DDI>=047451.000.441
L210FAZT+DDI>=071650.600.913
L210FABC+3TC>=059830.500.821
L210FTDF+3TC>=02505100.300.140
L210FTDF+FTC>=0130470.500.707
MutationNRTINNRTINumSeqNumMut% Mutantp
L210G008537240.00 
L210G>=1>=03810480.000.018
L210GAZT>=04720  
L210GDDI>=0540  
L210GD4T>=0550  
L210GABC>=0500  
L210GD4T+3TC>=045310  
L210GAZT+3TC>=0364810.000.506
L210GD4T+DDI>=04740  
L210GAZT+DDI>=07160  
L210GABC+3TC>=05980  
L210GTDF+3TC>=025050  
L210GTDF+FTC>=013040  
MutationNRTINNRTINumSeqNumMut% Mutantp
L210I0085372130.00 
L210I>=1>=038104110.000.172
L210IAZT>=04720  
L210IDDI>=0540  
L210ID4T>=0550  
L210IABC>=0500  
L210ID4T+3TC>=0453130.000.053
L210IAZT+3TC>=0364810.000.920
L210ID4T+DDI>=04740  
L210IAZT+DDI>=07160  
L210IABC+3TC>=059810.100.195
L210ITDF+3TC>=0250510.000.872
L210ITDF+FTC>=013040  
MutationNRTINNRTINumSeqNumMut% Mutantp
L210M00853725460.60 
L210M>=1>=038104890.200.000
L210MAZT>=04720  
L210MDDI>=0540  
L210MD4T>=0550  
L210MABC>=0500  
L210MD4T+3TC>=04531130.200.004
L210MAZT+3TC>=0364870.100.001
L210MD4T+DDI>=047420.400.762
L210MAZT+DDI>=071610.100.150
L210MABC+3TC>=059810.100.234
L210MTDF+3TC>=0250550.100.009
L210MTDF+FTC>=0130460.400.527
MutationNRTINNRTINumSeqNumMut% Mutantp
L210R008537260.00 
L210R>=1>=03810480.000.066
L210RAZT>=04720  
L210RDDI>=0540  
L210RD4T>=0550  
L210RABC>=0500  
L210RD4T+3TC>=045310  
L210RAZT+3TC>=0364810.000.685
L210RD4T+DDI>=04740  
L210RAZT+DDI>=07160  
L210RABC+3TC>=05980  
L210RTDF+3TC>=025050  
L210RTDF+FTC>=013040  
MutationNRTINNRTINumSeqNumMut% Mutantp
L210S00853722160.20 
L210S>=1>=0381042820.700.000
L210SAZT>=047210.200.777
L210SDDI>=0540  
L210SD4T>=0550  
L210SABC>=0500  
L210SD4T+3TC>=04531240.500.001
L210SAZT+3TC>=03648160.400.047
L210SD4T+DDI>=047410.200.781
L210SAZT+DDI>=07160  
L210SABC+3TC>=059850.800.016
L210STDF+3TC>=02505210.800.000
L210STDF+FTC>=0130440.300.916
MutationNRTINNRTINumSeqNumMut% Mutantp
L210T008537210.00 
L210T>=1>=038104180.000.000
L210TAZT>=04720  
L210TDDI>=0540  
L210TD4T>=0550  
L210TABC>=0500  
L210TD4T+3TC>=045310  
L210TAZT+3TC>=0364820.000.000
L210TD4T+DDI>=04740  
L210TAZT+DDI>=07160  
L210TABC+3TC>=05980  
L210TTDF+3TC>=025050  
L210TTDF+FTC>=013040  
MutationNRTINNRTINumSeqNumMut% Mutantp
L210V0085372290.00 
L210V>=1>=038104270.000.008
L210VAZT>=04720  
L210VDDI>=0540  
L210VD4T>=0550  
L210VABC>=0500  
L210VD4T+3TC>=0453120.000.956
L210VAZT+3TC>=0364810.000.803
L210VD4T+DDI>=047410.200.410
L210VAZT+DDI>=071620.200.014
L210VABC+3TC>=059820.300.006
L210VTDF+3TC>=0250510.000.697
L210VTDF+FTC>=0130410.000.944
MutationNRTINNRTINumSeqNumMut% Mutantp
L210W0085372590.00 
L210W>=1>=038104575615.100.000
L210WAZT>=0472336.900.000
L210WDDI>=054611.100.000
L210WD4T>=05559.000.000
L210WABC>=05012.000.013
L210WD4T+3TC>=045311352.900.000
L210WAZT+3TC>=036482045.500.000
L210WD4T+DDI>=0474316.500.000
L210WAZT+DDI>=071614019.500.000
L210WABC+3TC>=059840.600.000
L210WTDF+3TC>=02505180.700.000
L210WTDF+FTC>=0130440.300.008
MutationNRTINNRTINumSeqNumMut% Mutantp
L210Y0085372200.00 
L210Y>=1>=038104280.000.000
L210YAZT>=04720  
L210YDDI>=0540  
L210YD4T>=0550  
L210YABC>=0500  
L210YD4T+3TC>=0453110.000.660
L210YAZT+3TC>=036480  
L210YD4T+DDI>=04740  
L210YAZT+DDI>=071610.100.434
L210YABC+3TC>=05980  
L210YTDF+3TC>=025050  
L210YTDF+FTC>=013040  
Footnote: About one-half of the untreated isolates belong to non-subtype B isolates; About 20% of the treated isolates belong to non-subtype B isolates; A page containing summaries for all of the mutations at this position can be found here.

Genotype-phenotype correlation
Phenotypes of top 10 common patterns of drug resistance mutations with mutations at position 210.
Mutation patterns are listed in the frequency with which they have been reported in the published literature. The median level of fold resistance (compared with wildtype) for viruses with the mutation pattern in the first column are indicated when available. The subscripts indicate the number of viruses that were phenotyped. The drug susceptibility assay used was the PhenoSense assay (Monogram, South San Francisco). A hyperlink for each individual pattern is provided to access a complete list of mutations and fold resistances for each sequence matching the pattern of mutation.

A complete summary of additional in vitro susceptibility data for viruses with L210 obtained using other assays including the Antivirogram can be found here. A complete list of all mutation patterns with L210 (not just the top 10 most frequent patterns) can be found at this page.

Mutation PatternsNumber of
Sequences
AZT
foldn
TDF
foldn
ABC
foldn
3TC
foldn
41L,184V,210W,215Y138418511.6386.54820069
41L,67N,184V,210W,215Y127130531.6416.54620072
41L,67N,210W,215Y793401354.7255.3296.247
41L,210W,215Y755164213.1183.1192.834
41L,67N,69D,184V,210W,215Y48343281.8197.82620038
41L,67N,74V,184V,210W,215Y34711151.1149.31320022
41L,74V,184V,210W,215Y3455.0190.9178.11720030
41L,210W2780.520.721.121.24
41L,74I,184V,210W,215Y2661681.477.5820011
41L,67N,74I,184V,210W,215Y23421161.61410.01520025
Footnote: Mutation patterns were defined by the presence or absence of major NRTI drug resistance mutations ; Sequences containing a mixture at a major drug resistance positions were excluded; For the cutoffs defined by PhenoSense, open the sample report form provided on this page; The full list of all mutation patterns are also available here.

 

Phenotypic coefficients using machine learning
Least Square Regression (LSR) was used to learn the relative contribution of each mutation to the fold decrease in susceptibility for an ARV. The figure on the left (click to enlarge the figure) shows the regression coefficients (which correlate with the contribution to resistance) for the 23 nonpolymorphic NRTI-resistance mutations shown to contribute decreased susceptibility to at least one NRTI. A complete description of the method that generates this figure can be found at Rhee et al PNAS 2006.

 

Genotype-clinical outcome correlation
Studies correlating baseline genotype and virological response to an ARV therapy with or without mutations at 210.

ReferencePrevious NRTIFollow-up NRTIOther RxNo.PtsWeeksEffect of baseline mutations on response
Katlama(2000)>=2 NRTIs, (rare PI, NNRTI)Addition of ABCNone9216-48This study includes a subset of patients in the above analysis. M184V did not preclude an antiviral response. At week 16, 16/25 with M184V had RNA <=400 or RNA decrease of >=1 log.
Brun-Vezinet(2003)NRTI, PI, NNRTIABC as part of a new HAART regimenOB17512RNA decrease was -0.2 logs, -0.7 logs, and -1.6 logs in persons containing 5-6, 4, or <4 mutations at the following positions: 41, 67, 210, 215, 74, and 184.
Lanier(2004)>=2 NRTIs, (rare PI, NNRTI)Addition of ABCNone1664Meta-analysis of 5 intensification studies. Data on concomitant NNRTIs and PIs are not available. Median baseline RNA was 3.9 logs. 151/166 pts had >=1 NRTI mutation (usually TAMs and M184V). RNA decrease with (i) M184V alone >= 0.74 logs; (ii) 1 TAM >= 0.56 logs; (iii) M184V + 1 TAM >= 0.95 logs; (iv) 2-3 TAMs or 2 TAMs+ M184V >= ~0.35 logs; (v) M184V + 3 TAMs >= 0.18 logs; (vi) 4 TAMs >= 0.36 logs.
Winters(2003)NRTINRTI changeNFV, EFV, NFV/EFV10416-48In pts with isolates containing M184V substitution of ddI for 3TC was associated with a decreased risk of virologic failure (confirmed RNA >2000)
Frank(2004)0, 1, and 2 NRTIsddIHydroxy-urea13424Hydroxyurea + ddI led to a greater RNA decrease than ddI alone at week 8 (~1.8 vs 0.8 logs). The combination was associated with a sustained response ~1.2-1.6 logs at week 24. At week 8, there was a greater reduction in RNA in the NRTI-nave group (1.7 vs 1.2 logs) but there was little difference in response between those with M184V (1.2 logs in 18 3TC-experienced patients with M184V vs 1.4 logs in 61 3TC-nave patients).
Molina(2005)NRTI, PI, NNRTIAddition of ddINone1094Median overall response was 0.6 log RNA decrease. M184V alone >= 0.8 log RNA decrease. Pts with 0-1 TAMs >= 0.8-1.0 log RNA decrease (n=40); 2 TAMs >= 0.7 log RNA decrease (n=10); 3 TAMs >= 0.5 log RNA decrease (n=25); 4 TAMs >= 0.2 log RNA decrease (n=21). Median log RNA decrease in the presence of L74V (n=9) was 0.1 logs.
Sproat(2005)NRTI, PI, NNRTIddI as part of a new HAART regimenOB2814-48Observational study. Overall RNA decrease was 1.2, 1.0, 0.8, and 0.8 at weeks 4, 12, 24, and 48. There was no significant difference in RNA response between the 105 pts with and the 176 pts without M184V.
De Luca(2007)NRTI (including ddI in 76%) +/- NNRTI +/- PIddI as part of a new HAART regimenOB48512M41L, E44D/A/G, T69D/S/N/A, L210W, T215Y or T215 revertants, and L228H/R were associated with a reduced RNA decrease. D123E/N/G/S was associated with improved virological response. The following weighted score was derived: (M41L x 2) + E44D/A/G + T69D/S/N/A + (L210W x 2) + T215Y revertants + L228H/R - D123E/N/G/S. Relative to those with a score <=0, those with a score of 1 to 3 had a 0.34 decreased log RNA response and those with a score >=4 had a 0.68 decreased RNA log response.
Barrios(2003)NRTI, PI, NNRTITDF as part of a new HAART regimenOB15324Observational study. The presence of 41L, 210W, and 215Y were inversely associated with RNA response.
Masquelier(2004)NRTI, PI, NNRTITDF as part of a new HAART regimenOB16112Observational study. The strongest association with RNA decrease was the set of the 7 mutations: M41L, E44D, D67N, T69D/N/S, L74V, L210W, and T215Y/F : (i) <3 mutations >= median RNA reduction of -1.3 logs; (ii) 3-5 mutations >= median RNA reduction of 0.8 logs; (iii) >=6 mutations >= median increase of 0.1 logs. K65R and T69ins were not included because although they cause phenotypic resistance, there were insufficient pts with these mutations.
Miller(2004)NRTI, PI, NNRTIAddition of TDFNone22224-48Among pts receiving TDF, there was a mean 0.6 log RNA decrease at week 24 by ITT. Pts with 215Y/F alone had a 0.7 log RNA decrease. Pts with M41L+L210W + T215Y had a 0.2 log RNA decrease. Mutations at positions 67, 70, and 219 did not appear to affect response. K65R was present at baseline in 6 pts and was associated with lack of response. M184V was associated with a modest but significant improved response particularly in the absence of TAMs.
Abbreviations:
    OB - optimized background; TAM - thymidine analogue mutation (Type I: M41L, L210W, T215Y; Type II: D67N, K70R, T215F, K219Q/E;);

References:
  • Katlama C., Clotet B., Plettenberg A., Jost J., Arasteh K., Bernasconi E., Jeantils V., Cutrell A., Stone C., Ait-Khaled M., Purdon S. The role of abacavir (ABC, 1592) in antiretroviral therapy-experienced patients: results from a randomized, double-blind, trial. CNA3002 European Study Team. AIDS. 2000 May 5;14(7):781-9.
  • Brun-Vezinet F., Descamps D., Ruffault A., Masquelier B., Calvez V., Peytavin G., Telles F., Morand-Joubert L., Meynard J.L., Vray M., Costagliola D. Clinically relevant interpretation of genotype for resistance to abacavir. AIDS. 2003 Aug 15;17(12):1795-802.
  • Lanier E.R., Ait-Khaled M., Scott J., Stone C., Melby T., Sturge G., St Clair M., Steel H., Hetherington S., Pearce G., Spreen W., Lafon S. Antiviral efficacy of abacavir in antiretroviral therapy-experienced adults harbouring HIV-1 with specific patterns of resistance to nucleoside reverse transcriptase inhibitors. Antivir Ther. 2004 Feb;9(1):37-45.
  • Winters M.A., Bosch R.J., Albrecht M.A., Katzenstein D.A. Clinical impact of the M184V mutation on switching to didanosine or maintaining lamivudine treatment in nucleoside reverse-transcriptase inhibitor-experienced patients. J Infect Dis. 2003 Aug 15;188(4):537-40.
  • Frank I., Bosch R.J., Fiscus S., Valentine F., Flexner C., Segal Y., Ruan P., Gulick R., Wood K., Estep S., Fox L., Nevin T., Stevens M., Eron J.J. Jr. Activity, safety, and immunological effects of hydroxyurea added to didanosine in antiretroviral-naive and experienced HIV type 1-infected subjects: a randomized, placebo-controlled trial, ACTG 307. AIDS Res Hum Retroviruses. 2004 Sep;20(9):916-26.
  • Molina J.M., Marcelin A.G., Pavie J., Heripret L., De Boever C.M., Troccaz M., Leleu G., Calvez V.. Didanosine in HIV-1-infected patients experiencing failure of antiretroviral therapy: a randomized placebo-controlled trial. J Infect Dis. 2005 Mar 15;191(6):840-7.
  • Sproat M., Pozniak A.L., Peeters M., Winters B., Hoetelmans R., Graham N.M., Gazzard B.G. The influence of the M184V mutation in HIV-1 reverse transcriptase on the virological outcome of highly active antiretroviral therapy regimens with or without didanosine. Antivir Ther. 2005;10(2):357-61.
  • De Luca A., Giambenedetto S.D., Trotta M.P., Colafigli M., Prosperi M., Ruiz L., Baxter J., Clevenbergh P., Cauda R., Perno C.F., Antinori A. Improved interpretation of genotypic changes in the HIV-1 reverse transcriptase coding region that determine the virological response to didanosine. J Infect Dis. 2007 Dec 1;196(11):1645-53.
  • Barrios A., de Mendoza C., Martin-Carbonero L., Ribera E., Domingo P., Galindo M.J., Galvez J., Estrada V., Dalmau D., Asensi V., Soriano V. Role of baseline human immunodeficiency virus genotype as a predictor of viral response to tenofovir in heavily pretreated patients. Clin Microbiol. 2003 Sep;41(9):4421-3.
  • Masquelier B., Tamalet C., Montes B., Descamps D., Peytavin G., Bocket L., Wirden M., Izopet J., Schneider V., Ferre V., Ruffault A., Palmer P., Trylesinski A., Miller M., Brun-Vezinet F., Costagliola D. Genotypic determinants of the virological response to tenofovir disoproxil fumarate in nucleoside reverse transcriptase inhibitor-experienced patients. Antivir Ther. 2004 Jun;9(3):315-23.
  • Miller M.D., Margot N., Lu B., Zhong L., Chen S.S., Cheng A., Wulfsohn M. Genotypic and phenotypic predictors of the magnitude of response to tenofovir disoproxil fumarate treatment in antiretroviral-experienced patients. J Infect Dis. 2004 Mar 1;189(5):837-46.